ERK activation upon hypoxia: involvement in HIF-1 activation

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by h ypoxia, The HIF-1 activation transduction pathway is poorly understood. In this report, we investigated the activation of extracellular regulated kina ses (ERK) in hypoxia and their involvement in HIF-1 activation. We demonstr ated that in human microvascular endothelial cells-1 (HMEC-1), ERK kinases are activated during hypoxia, Using dominant negative mutants, we showed th at ERK1 is needed for hypoxia-induced HIT-1 transactivation activity. Moreo ver, using a kinase assay and Western blot experiments, we showed that HIF- 1 alpha is phosphorylated in hypoxia by an ERK-dependent pathway. These res ults evidence the role of mitogen-activated protein kinase in the transcrip tional response to hypoxia, (C) 2000 Federation of European Biochemical Soc ieties.